This invention relates to dihydroxybenzoic acid derivatives. More particularly, the invention relates to 2,5-dihydroxybenzoic acid derivatives, compositions containing same, and the topical and systemic, especially oral, use thereof with animals, including humans, to provide an analgesic and anti-inflammatory effect.
Tissue inflammation is the result of interconnected physiological events. Inflammation of the skin which is associated with tissue damage can result from various skin disorders such as eczema, psoriasis, seborrheic dermatitis, contact dermatitis, allergic dermatitis, etc. Inflammation is also associated with tissue damage resulting from ultraviolet or thermal burns, attack by certain microorganisms, insect bites, stings, etc. Inflammation of deeper structures, the muscles, tendons, bursa and joints, which is associated with tissue damage, can result from physical trauma, e.g., sprains, strains, contusions, strenuous exercise, etc. Such inflammation may result in bursitis, tendinitis, and muscle soreness. Inflammation and pain are also associated with tissue damage resulting from metabolic disorders, such as gout, or from immunologic disorders, such as rheumatoid arthritis, or from changes associated with aging, such as osteoarthritis.
Symptoms of inflammation are erythema (redness), edema (swelling), heat, pain, and loss of function. The immediate consequence of tissue damage is the release of certain chemical agents which are mediators of inflammation, i.e. these materials evoke and intensify the events which result in the redness, swelling, pain and heat. Examples of these chemical agents are histamine, serotonin and the kinins.
Among the important mediators of inflammation are certain prostaglandins. In contrast to histamine, serotonin and the kinins, the prostaglandins are continuously biosynthesized and released from cells at the inflammatory site. Thus, the prostaglandins have a longer lasting effect. Various anti-inflammatory compounds are known inhibitors of prostaglandin synthesis. One commonly used anti-inflammatory/analgesic drug is aspirin. Aspirin, of course, is a well known oral drug. However, when administered orally, aspirin is known to cause gastric irritation and frank stomach bleeding in up to 70% of patients using aspirin-based products. Recent studies have also indicated aspirin can delay and decrease inflammation in humans when applied topically. However, it has been found that a relatively high concentration of aspirin must be topically applied before its effect as a topical analgesic is noted. Unfortunately, the repeated topical application of a high level of aspirin causes primary irritation and peeling of the superificial layers (the stratum corneum) of the skin.
Accordingly, there is a continuing need for analgesic/antiinflammatory agents which can be used orally or topically without adverse secondary effects.
It is an object of this invention to provide compounds which are useful as analgesic and anti-inflammatory agents.
It is another object of this invention to provide compounds which can be systemically and topically administered to provide an analgesic effect and to alleviate inflammation.